This research project proposes to attempt to answer the following questions: Is it possible to induce and recover mutations that specifically regulate the level of activity of a specific enzyme during development in Drosophila? If so, where are these mutant genes located in the genome relative to the structural locus of the enzyme subject to control? By what mechanism(s) do the wild type alleles of these mutants control the level of enzyme activity? Are other enzymes with similar ontogenetic patterns of enzyme activity subject to control by these same genes? The proposed target enzyme is dopa decarboxylase, which has been shown to have three (possibly four) distinct peaks of activity during development in Drosophila and in Calliphora is known to be inducible by ecdysone. Using EMS as a mutagen, this research proposes to screen for a series of mutations on all four chromosomes which are either resistant or hypersensitive to one or more specific inhibitors in dopa decarboxylase. It is thought that some of the resistant strains may either have higher than wild type levels of dopa decarboxylase activity or show constitutive enzyme activity throughout development and that some of the hypersensitive strains may exhibit repressed levels of activity throughout development or are mutations of the structural locus. Also an attempt will be made to recover mutations which are insensitive to induction by ecdysone, again using specific inhibitors of dopa decarboxylase as a screening device. When interesting mutants have been recovered, they will be located in the genome and experiments will be carried out to determine if changes in the level of enzyme activity are due to changes in the rate of enzyme synthesis, changes in the rate of degradation, or to changes in the level of specific inhibitors or activators. In addition the effect of these mutations on the level of activity of other enzymes will be analyzed. BIBLIOGRAPHIC REFERENCES: Wright, T.R.F., R.B. Hodgetts, and A.F. Sherald. The genetics of dopa decarboxylase in Drosophila melanogaster. I. Isolatio and characterization of deficiencies of the structural locus and the alpha-methyl dopa hypersensitive locus. Submitted to Genetics, in press.